Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance.

BACKGROUND: Recent studies suggest that the late phase of ischemic preconditioning (PC) can be mimicked by pretreatment with NO donors. The ability of clinically relevant NO donors to induce PC against infarction, however, has not been evaluated. Furthermore, it is unknown whether tolerance to the hemodynamic actions of nitrates also extends to their PC effects. METHODS AND RESULTS: Conscious rabbits underwent a 30-minute coronary occlusion and 3 days of reperfusion. A 60-minute intravenous (IV) infusion of nitroglycerin (NTG) ending 1 hour before occlusion reduced infarct size, indicating an early PC effect. When the time interval between NTG infusion and occlusion was extended to 24 or 72 hours, the infarct-sparing action of NTG became even more pronounced, indicating a robust late PC effect. Transdermal NTG patches elicited a late PC effect that was (1) equivalent to that induced by IV NTG, demonstrating the efficacy of transdermal NTG as an alternative form of NTG delivery for inducing late PC, and (2) similar in nitrate-tolerant and -nontolerant rabbits, demonstrating that tolerance does not extend to the PC effects of NTG. CONCLUSIONS: In conscious rabbits, administration of NTG via either the IV or the transdermal route elicits a robust protective effect against infarction that lasts for 72 hours. The magnitude of NTG-induced cardioprotection is equivalent to that observed during the late phase of ischemic PC and is not affected by the development of tolerance. These findings reveal a new action of nitrates and support novel applications of these drugs for protecting the ischemic myocardium in patients.

Nitroglycerin induces late preconditioning against myocardial stunning via a PKC-dependent pathway.

Previous studies have shown that administration of nitric oxide (NO) donors induces a delayed cardioprotective effect indistinguishable from the late phase of ischemic preconditioning (PC). However, the ability of clinically relevant NO donors to elicit this phenomenon has not been evaluated. In this study we tested whether an NO-releasing agent that is nitroglycerin (NTG), which is widely used clinically, can mimic the late phase of ischemic PC. Four groups of conscious rabbits underwent six cycles of 4-min occlusion (O)/4-min reperfusion (R) for 3 consecutive days (days 1, 2, and 3). The severity of myocardial stunning was assessed as the total deficit of systolic wall thickening (WTh) after the last O/R cycle. In the control group (group I, n = 6), the total deficit of WTh was reduced by 50% and 51% on days 2 and 3 vs. day 1, respectively, indicating late PC against stunning. Pretreatment with NTG (2 microg. kg(-1). min(-1) iv over 1 h) on day 0 (group II, n = 6) was as effective as ischemic PC in mitigating myocardial stunning 24 h later (day 1); on days 2 and 3, no further reduction of stunning was seen. Coadministration of the PKC inhibitor chelerythrine (5 mg/kg) with NTG (group III, n = 6) completely abrogated the NTG-induced protection. Pretreatment with chelerythrine alone (group IV, n = 5) did not alter stunning. These results demonstrate that a relatively brief infusion of NTG induces a robust protective effect against stunning 24 h later via a protein kinase C (PKC)-dependent signaling mechanism. The magnitude of NTG-induced protection is equivalent to that observed during the late phase of ischemic PC. Late PC induced by brief treatment with NTG could be a useful therapeutic strategy for myocardial protection in patients with ischemic heart disease.

Degradation-induced transmission losses in silica optical fibers.

BACKGROUND AND OBJECTIVE: The interaction of surgical optical fibers with tissue has been studied. STUDY DESIGN/METHODS AND MATERIALS: Fibers (600 microns) were lased in chicken and beef tissue using a Nd:YAG laser from 5 to 50 W in both cw and pulsed modes. RESULTS: With longer lasing and higher power, larger transmission loss and degradation (burn-in) of the fiber tip, occurred. This degradation converts the Nd:YAG laser power to heat and leads to further energy loss. During contact lasing, tissue and blood adhere to the fiber tip surface limiting laser transmission, desiccating, and eventually destroying adhering tissues. Such tissue residues create high power densities and temperatures at the tip, which then cause a variety of degradation processes to be initiated. CONCLUSION: "Burned-in" fibers do not photocoagulate; rather they incise tissue. With continued lasing, thermal shock, chemical, and mechanical breakdown of the fiber leads to failure of the fiber tip and the spalling of glass fragments into the tissue bed.

The use of low-viscosity fluids for hysteroscopy.

We reviewed the literature addressing the use and complications associated with low-viscosity distention fluids in urologic and hysteroscopic procedures. The possible causes of fluid complications included elevated intrauterine pressure, myometrial invasion, prolonged operating time, and operative trauma to the cervix or uterine body. Physiologic electrolyte solutions create only fluid overload, and treatment requires cardiovascular support and diuresis. Nonelectrolytic solutions result in acute dilutional hyponatremia, which has been referred to as the transurethral resection of the prostate syndrome. Treatment requires diuresis and a rapid, controlled return of the serum sodium level to 120-130 mmol. These complications can be minimized with proper use of equipment and careful monitoring of fluid volumes. To recognize and treat them, the surgeon must be knowledgeable about the fluid being used and the difficulties it may cause.

The relationship of different power settings and fiber geometries to thermal tissue damage created by the superpulse Nd:YAG laser.

We attempted to quantify the amount of thermal damage that was created to surrounding tissues when an incision was made with the superpulse neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with the optical fiber in contact. Light micrographic studies of several incisions, at different laser power settings and with different fiber geometries, were made in the anterior abdominal wall of 16 Sprague-Dawley rats. The specimens were collected immediately postoperatively and at 48 hours postoperatively. Several laser power settings (2-50 W) and seven different optical fiber geometries were studied. The micrographs showed minimal damage (<0.1 mm) to surrounding tissues at all laser power settings in both the immediate and the 48-hour studies. The superpulse Nd:YAG laser with optical fiber contact limited laser thermal damage to the surrounding tissues to less than 0.1 mm in the range of power settings studied. Higher power settings minimally increased the damage. The geometries of the optical fiber created no significant alteration in thermal damage. The results suggest that the superpulse Nd:YAG laser creates both thermal and photodisruptive effects in tissue.

Control of intrauterine fluid pressure during operative hysteroscopy.

STUDY OBJECTIVE: To evaluate the safety of a commonly used piston pump that controls the infusion pressure of low-viscosity fluids in a continuous-flow hysteroscopic system during operative hysteroscopy. DESIGN: Consecutive patients requiring operative hysteroscopy. SETTING: Three hospital facilities in the Midwest. PATIENTS: Sequential sample of 250 women who underwent operative hysteroscopy. INTERVENTIONS: Endometrial ablations, resection of submucosal or pedunculated uterine leiomyomata with or without endometrial ablation, polyp resections, metroplasty, and lysis of synechiae. MEASUREMENTS AND MAIN RESULTS: The most serious complication of operative hysteroscopy is fluid overload due to intravasation into the patient's vascular system. Low-viscosity fluids were infused by the Zimmer Controlled Distention Irrigation System. The instrument uses a closed-feedback loop to monitor cavity pressure and automatically regulates the flow to maintain the set point pressure. It is designed to operate in a pressure range of 0 to 80 mm Hg and at flows in excess of 450 ml/minute. In 250 operative hysteroscopies no fluid complications occurred when intrauterine pressure was maintained below 80 mm Hg. No clinically significant differences in intravasation were seen in any type of operative hysteroscopy. CONCLUSIONS: This controlled mechanical pump system with exact intrauterine pressure measurement reduced many technical difficulties associated with low-viscosity media, and created a safe environment for the media's use in operative hysteroscopy.

Attempted transcervical occlusion of the fallopian tube with the Nd:YAG laser.

A prospective multi-center trial was initiated to test the efficacy and safety of transcervical occlusion of the fallopian tube with the Nd:YAG laser. A multi-center approach was deemed necessary because of the large sample size required to test adequately the effectiveness of sterilization procedures. However, efforts to continue the study as designed were abandoned because, of the 17 subjects completing the study, only four (24%) had bilateral tubal occlusion at the site of laser treatment. We conclude that the hysteroscopic method, as tested, is inadequate to provide permanent sterilization. Modification of the technique or alterations in patient preparation may improve the outcome.

Comparison of tissue effects with sculptured fiberoptic cables and other Nd:YAG laser and argon laser treatments.

The use of a fiber optic cable in contact with tissue results in a complex thermal interaction between the cable and the tissue. The effect of the laser-tissue interaction was investigated using sculptured quartz fiber optic cables, sapphire contact rods, and bare fiber optic cables attached to the Nd:YAG laser. The laser-tissue effects of the Nd:YAG and argon lasers were compared. Examination of treated animals showed there to be a significant difference between immediate and 48-hour thermal effects. The sculptured fibers created significantly less tissue damage than the sapphire contact tips, the 0.6-mm bare fiber, or the argon laser with a 0.3-mm bare fiber either with or without contact. All Nd:YAG laser contact treatments were less damaging than the argon laser treatments.

Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions.

A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions.

Use of the Nd:YAG laser for the treatment of endometriosis.

Thirty-eight patients had laparoscopic treatment of endometriosis by the use of the Nd:YAG laser, combined with a fiber-optic cable equipped with sapphire contact tips. In this preliminary investigative study patients in all four revised American Fertility Society classifications were treated for both gynecologic disability and infertility. The analysis of the parameters studied for gynecologic disability indicated significant clinical improvement. The 18 patients with associated infertility had a conception rate of 67% for all stages of infertility. The study shows that the Nd:YAG laser used laparoscopically with the sapphire contact tip is safe and that its efficacy compares with that of other conservative surgical modalities.

A second puncture probe for laparoscopic delivery of the Nd:Yag laser.

A prospective trial was initiated to determine the efficiency and safety of a laparoscopic second puncture probe designed to deliver the Nd:Yag laser. A contact technique was used to treat 32 women with either endometriosis (N = 23) or post-inflammatory pelvic adhesions (N = 9). The delivery system proved to be safe and provided easy access to all areas of pelvic pathology. The potential advantages over the CO2 laser include improved hemostasis, decreased plume formation, the ability to incise adhesions safely without a backstop, and effective transmission of the laser energy through fluids.